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https://observatorio.fm.usp.br/handle/OPI/2398
Título: | GATA-6 and NF-kappa B Activate CPI-17 Gene Transcription and Regulate Ca2+ Sensitization of Smooth Muscle Contraction |
Autor: | BOOPATHI, Ettickan; HYPOLITE, Joseph A.; ZDERIC, Stephen A.; GOMES, Cristiano Mendes; MALKOWICZ, Bruce; LIOU, Hsiou-Chi; WEIN, Alan J.; CHACKO, Samuel |
Citación: | MOLECULAR AND CELLULAR BIOLOGY, v.33, n.5, p.1085-1102, 2013 |
Resumen: | Protein kinase C (PKC)-potentiated inhibitory protein of 17 kDa (CPI-17) inhibits myosin light chain phosphatase, altering the levels of myosin light chain phosphorylation and Ca2+ sensitivity in smooth muscle. In this study, we characterized the CPI-17 promoter and identified binding sites for GATA-6 and nuclear factor kappa B (NF-kappa B). GATA-6 and NF-kappa B upregulated CPI-17 expression in cultured human and mouse bladder smooth muscle (BSM) cells in an additive manner. CPI-17 expression was decreased upon GATA-6 silencing in cultured BSM cells and in BSM from NF-kappa B knockout (KO) mice. Moreover, force maintenance by BSM strips from KO mice was decreased compared with the force maintenance of BSM strips from wild-type mice. GATA-6 and NF-kappa B overexpression was associated with CPI-17 overexpression in BSM from men with benign prostatic hyperplasia (BPH)-induced bladder hypertrophy and in a mouse model of bladder outlet obstruction. Thus, aberrant expression of NF-kappa B and GATA-6 deregulates CPI-17 expression and the contractile function of smooth muscle. Our data provide insight into how GATA-6 and NF-kappa B mediate CPI-17 transcription, PKC-mediated signaling, and BSM remodeling associated with lower urinary tract symptoms in patients with BPH. |
Aparece en las colecciones: | Artigos e Materiais de Revistas Científicas - HC/IOT Artigos e Materiais de Revistas Científicas - LIM/55 |
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art_GOMES_GATA_6_and_NF_kappa_B_Activate_CPI_2013.PDF Restricted Access | publishedVersion (English) | 3.84 MB | Adobe PDF | Visualizar/Abrir Request a copy |
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